Intestinal uptake, metabolism, and transport of naphthol: In vitro capacity, requirements, and inhibition

Abstract

The metabolism and transport of [ 14C]-naphthol were investigated in sacs of rat small intestine to better understand metabolism of the pesticide carbaryl (which contains naphthol) in the intestine. The capacity to synthesize polar 14C-labeled metabolites was approximately saturated at 50 μ M naphthol. The metabolic capacity of the cranial small intestine was about two times the capacity of the caudal. Anaerobic incubation severely suppressed naphthol metabolism. Sodiumfree medium suppressed metabolism only slightly but altered transport of water and of the polar 14C-labeled metabolites to serosal and mucosal fluids; the effect on metabolite transport cannot be explained by the effects of sodium on water movements, however. Calcium-free medium did not affect metabolism or metabolite transport; 2,4-dinitrophenol, and possibly phlorizin, but not ouabain, suppressed naphthol metabolism in specific regions of the intestine. Each of the three inhibitors altered metabolite transport. It is concluded that the capacity to conjugate naphthol in the small intestine is greater in the cranial than caudal regions; the quantity of naphthol taken up from the medium is proportional to the rate of formation of the polar metabolite, naphthyl glucuronide; addition of 2,4-dinitrophenol, phlorizin, or ouabain, or deletion of sodium, perturbed the transport of the polar metabolite, but the perturbance could not be explained by the effect on rate or direction of fluid transfer and indicated an effect on cellular permeability or on transport mechanisms; the effect of the three inhibitors and possibly of elevated naphthol concentrations (to 520 μ M) in the medium on metabolite transport may be by a sodium interaction; the latter suggests that naphthol may be toxic to the intestine at concentrations approaching 100 to 1000 μ M.